The proposed project encompasses several areas of investigation into the function of metals and biological systems. The mechanisms of action of bovine carboxypeptidase A and horse liver alcohol dehydrogenase are being studied using steady state and rapid kinetic techniques, EPR, and chemical modifications. Concomitantly, the biochemistry and enzymology of human carboxypeptidases and human liver alcohol dehydrogenase are being examined from a functional and medical point of view. The role of metals, and particularly zinc, in human health and disease in general, as well as in normal and leukemic leukocyte proliferation, is being studied. The application of laser resonance raman spectroscopy to the study of proteins in general, and in particular, carboxypeptidase A, is continuing. The extension of the use of lanthanide ions as macro molecular probes for distance measurements in proteins is being expanded. The use of stopped-flow and temperature jump techniques for the investigation of the elementary steps in enzyme catalysis continues. The application of the latest spectroscopic techniques for metal measurements in biological systems are being assessed. Finally, the theory of enzyme kinetics in the crystalline state is being derived from the measurements already made on the carboxypeptidases and other enzyme systems.